1. Field of the Invention
This invention relates generally to magnetic therapeutic systems and methods, and specifically, to systems and methods for using magnetic fields to contain magnetizable therapeutic, diagnostic or prophylactic agents in a target volume within a patient's body, or to move such magnetizable agents through a target volume within a patient's body.
2. Description of Related Art
Cancer is a major cause of death in the United States, claiming more than 500,000 lives each year according to American Cancer Society estimates. The primary treatment options for cancer are surgery, radiation therapy, chemotherapy, and immunotherapy. Although surgical removal of a primary tumor is usually the favored option, some tumors are inoperable, for example because they are inaccessible or have ill-defined borders. Thus, radiation therapy, chemotherapy, and immunotherapy are often used to treat cancer in conjunction with, or instead of, surgery. In later (metastatic) stages of disease, the patient can have multiple metastatic tumor foci that range in size from microscopic to grossly visible, and includes metastases in unknown anatomical locations. In these cases one-by-one removal of tumors is not feasible and thus surgery is not an effective clinical strategy. For patients with metastatic disease, radiation therapy to regions of the body that contain large/detectable metastic tumors, systemic chemotherapy, and immunotherapy are the usual remaining options.
Radiation therapy, chemotherapy, and immunotherapy can achieve some success in treating cancer, but these treatments have disadvantages as well. For example, radiation therapy usually treats only a specific small region of the body and there may be metastatic tumors outside this region. Moreover, hypoxic cancer cells in solid tumors are less prone to the DNA damage caused by radiation, and therefore can be resistant to radiation therapy. Immunotherapy also has disadvantages, in that non-tumor cells can be damaged by the treatment, delivery to tumor cells may be inefficient, clinical efficacy may be low, and toxicity may be unacceptably high. Chemotherapy remains a primary treatment for cancer, but also has disadvantages, including poor delivery and cellular uptake of chemotherapeutic agents into malignant tissue, drug resistance and non-specific toxicity. Further, the dosage of chemotherapeutic agents is usually limited to a dosage that the patient can withstand, however such a dosage may not be high enough to effectively treat all or even the majority of malignant cells.
Poor delivery of therapeutic agents to diseased cells is a difficult problem in cancer treatment, especially treatment of cancers that have spread widely, including lesions that are deep within the body. Even when the agents are delivered to the locale of a tumor mass, poor penetrability into the tumor mass may require prolonged high dose treatment, and subsequent severe systemic adverse effects. For these reasons, it is desirable to provide improved and alternative techniques for treating disease, particularly techniques that are less invasive and traumatic to the patient than those currently in practice. The promise of targeted drug delivery is that therapeutic agents can be targeted to diseased tissue, thereby enabling high concentrations in tumors, with lower concentrations elsewhere in the body. This promise can be effected by targeting a specific region or volume in the patient that likely contains the majority of cancer metastases that would cause morbidity and mortality if left unchecked, but whose specific location, number, and properties are not known in detail. For example, it is known that breast cancer usually metastasizes to the lungs and liver, thus an ability to confine chemotherapy to the upper torso would likely provide improved clinical efficacy while minimizing the side-effects of chemotherapy in the rest of body (for example, sparing the immune system and bone marrow in regions outside the upper torso). In many cancers, such a treatment could address the majority of clinically relevant tumors. Although it would not eliminate the entire tumor burden in a patient it would effectively treat the most clinically problematic tumor foci and thereby change the disease from a death sentence into a chronic, manageable condition. Such targeted drug delivery to specific anatomical regions of the body is thus potentially valuable but has not been achieved using current targeted delivery techniques; methods and systems to achieve this goal are the subject of the current patent.
The ability to focus therapeutic agents to specific locations is useful not only for cancer treatment, but also for the treatment of diseases or disorders that are localized in the body, for example a localized infection such as a spinal abscess, or as a second example, restenosis in a coronary artery. Targeted delivery techniques are being explored for the treatment of cancers and other diseases, and include three primary approaches: passive targeting, active targeting, and physical targeting. Passive targeting techniques rely on selective accumulation of drugs at the tumor site due to differences between healthy and tumor cells, for example the Enhanced Permeability and Retention (EPR) effect, or on localized delivery, for example direct intratumoral delivery in prostate cancer treatment. Active targeting techniques include conjugating the therapeutic agent to a targeting ligand, such as RGD peptides, and tumor-specific antibodies. Physical targeting techniques include stimulating target tumor tissue with ultrasonic waves, which promotes intracellular drug uptake.
Magnetic drug delivery has also been attempted, in which drugs are attached to magnetic particles, and then magnetic fields from stationary magnets outside the body are used to focus the drugs to specific locations near the surface of the body. Magnetic drug particles for treatment of shallow tumors have been tested for safety and efficacy in animal and human clinical trials, where particles are injected into a vein, distributed throughout the body by the circulatory system, and then captured and concentrated at the desired shallow tumor location by a strong stationary magnet held near the tumor. Direct injection of magnetic particles into a tumor, followed by thermal excitation of the magnetic particles, has also been attempted with some success in the treatment of prostate cancers. However, non-invasive magnetic drug delivery to deep tissue such as the lungs, intestines, and liver, has not been successful because the magnetic fields necessary to overcome blood flow rates in the arteries, and to target the nanoparticles more than about 5 centimeters inside the body, generally exceed the threshold (˜1-8 Tesla) of what is considered safe for human application. Thus, conventional magnetic drug targeting has not proven successful with deep tissue tumors. The above depth limit also means that it is not currently possible to magnetically confine treatment to a desired target volume that includes deep regions. For example, it is not possible to confine drugs to the entirety of the lungs, liver, or upper torso including its deep-in-the-body portions. Thus current magnetic drug delivery cannot focus treatment to the majority of cancer metastases that will cause morbidity and mortality if left untreated and whose numbers, properties, and anatomic locations are unknown but are still often largely confined to a specific volume of the body (even in late and advanced stages of the disease).
What is needed are improved magnetic drug delivery methods and systems that overcome these difficulties and results in improved therapeutic, diagnostic or prophylactic use of magnetic agents, particularly for treatment of desired target volumes that include deep regions and many hard to access metastatic tumors whose exact location is not known.